Effect of selective phosphodiesterase inhibitors on response of ovine pulmonary arteries to prostaglandin E2

Gao, Yuansheng, Jean-François Tolsa, Hai Shen, and J. Usha Raj. Effect of selective phosphodiesteraseinhibitors on response of ovine pulmonary arteries to prostaglandinE₂. J. Appl. Physiol. 84(1): 13-18, 1998.Several adenosine3,5-cyclic monophosphate (cAMP)-hydrolyzingphosphodiesterase isozymes are present in the pulmonary vasculature.The present study was designed to determine the effect of selectiveinhibitors of phosphodiesterase subtypes on prostaglandinE₂(PGE₂)-induced relaxation ofisolated fourth- generation pulmonary arteries of newborn lambs.PGE₂ and forskolin causedpulmonary arteries to relax and induced an increase in theintracellular cAMP content in the vessels. The relaxation and change incAMP content were augmented by milrinone and rolipram, inhibitors ofphosphodiesterase type 3 (PDE3) and type 4 (PDE4), respectively. Theaugmentation in relaxation and the increase in cAMP content caused bymilrinone plus rolipram was greater than the sum of theresponses caused by either of the inhibitors alone.8-Methoxymethyl-1-methyl-3-(2-methylpropyl)xanthine, an inhibitor of phosphodiesterase type 1, had no effect on relaxation andchange in cAMP induced by PGE₂ andforskolin. Acetylcholine alone had no effect on cAMP content in thevessels but augmented the relaxation and the increase in cAMP inducedby PGE₂ and forskolin in arterieswith endothelium. This effect was not observed in arteries withoutendothelium or in arteries with endothelium treated withN^G-nitro-L-arginine.These results suggest that PDE3 and PDE4 are the primary enzymeshydrolyzing cAMP of pulmonary arteries of newborn lambs and that aninhibition of both PDE3 and PDE4 would result in a greater effect thanthat caused by inhibition of either one of the subtype isozymes alone.Furthermore, endothelium-derived nitric oxide may enhance cAMP-mediatedrelaxation by inhibition of PDE3.

     

High regenerative nature ofMentha arvensis internodes

Media and incubation conditions have been defined for highly efficient regeneration of shoots from internode explants of slow and fast growing cultivars ofMentha arvensis. Internodal segments excised from thein vitro raised shoots were inoculated on the MS medium supplemented with combinations of 5 concentrations of l-napthalene acetic acid (NAA) and 3 concentrations of 6-benzyl amino purine (BAP). The media containing 2 μg ml⁻¹ NAA, 10 Μg ml⁻¹ BAP and 1 μg ml⁻¹ NAA, 5 μg ml⁻¹ BAP proved best for shoot regeneration and growth responses on cv Himalaya and cv Kalka explants, respectively. In 12 weeks time, on average one explant of cv Himalaya produced about 200 shoots and that of cv Kalka produced about 180 shoots. The Himalaya explants required higher concentrations of NAA and BAP for high efficiency proliferation as compared to the Kalka explants. The experiments demonstrated that internodal tissue inMentha arvensis can be induced to obtain direct shoot regenerants with high efficiency. The analysis of the RAPD profiles of 100 regenerated plantlets each of cv Himalaya and Kalka showed more than 99.9% homogeneity in bands with respect to the parents.     

Individual and Facility-Level Determinants of Iron and Folic Acid Receipt and Adequate Consumption among Pregnant Women in Rural Bihar,India

Background

In Bihar, India, high maternal anemia prevalence and low iron and folic acid supplement (IFA) receipt and consumption have continued over time despite universal IFA distribution and counseling during pregnancy.

Purpose

To examine individual and facility-level determinants of IFA receipt and consumption among pregnant women in rural Bihar, India.

Methods

Using District Level Household Survey (2007–08) data, multilevel modeling was conducted to examine the determinants of two outcomes: IFA receipt (any IFA receipt vs. none) and IFA consumption (≥90 days vs. <90 days). Individual-level and facility-level factors were included. Factor analysis was utilized to construct antenatal care (ANC) quality and health sub-center (HSC) capacity variables.

Results

Overall, 37% of women received any IFA during their last pregnancy. Of those, 24% consumed IFA for 90 or more days. Women were more likely to receive any IFA when they received additional ANC services and counseling, and attended ANC earlier and more frequently. Significant interactions were found between ANC quality factors (odds ratio (OR): 0.37, 95% confidence interval (CI): 0.25, 0.56) and between ANC services and ANC timing and frequency (OR: 0.68, 95% CI: 0.56, 0.82). No HSC factors were significantly associated with IFA receipt. Women were more likely to consume IFA for ≥90 days if they attended at least 4 ANC check-ups and received more ANC services. IFA supply at the HSC (OR: 1.37, 95% CI: 1.04, 1.82) was also significantly associated with IFA consumption.

Conclusions

Our findings indicate that individual and ANC factors (timing, frequency, and quality) play a key role in facilitating IFA receipt and consumption. Although HSC capacity factors were not found to influence our outcomes, significant variation at the facility level indicates unmeasured factors that could be important to address in future interventions.     

Socio-Economic Differentials in Impoverishment Effects of Out-of-Pocket Health Expenditure in China and India: Evidence from WHO SAGE

Background and Objectives

The provision of affordable health care is generally considered a fundamental goal of a welfare state. In addition to its role in maintaining and improving the health status of individuals and households, it impacts the economic prosperity of a society through its positive effects on labor productivity. Given this context, this paper assesses socioeconomic-differentials in the impact of out-of-pocket-health-expenditure (OOPHE) on impoverishment in China and India, two of the fastest growing economies of the world.

Data and Methods

The paper uses data from the World Health Organisation’s Study on Global Ageing and Adult Health (WHO SAGE), and Bivariate as well as Multivariate analyses for investigating the socioeconomic-differentials in the impact of out-of-pocket-health-expenditure (OOPHE) on impoverishment in China and India.

Results and Conclusions

Annually, about 7% and 8% of the population in China and India, respectively, fall in poverty due to OOPHE. Also, the percentage shortfall in income for the population from poverty line due to OOPHE is 2% in China and 1.3% in India. Further, findings from the multivariate analysis indicate that lower wealth status and inpatient as well as outpatient care increase the odds of falling below poverty line significantly (with the extent much higher in the case of in-patient care) due to OOPHE in both China and India. In addition, having at least an under-5 child in the household, living in rural areas and having a household head with no formal education increases the odds of falling below poverty line significantly (compared to a head with college level education) due to OOPHE in China; whereas having at least an under-5 child, not having health insurance and residing in rural areas increases the odds of becoming poor significantly due to OOPHE in India.     

Adaptive laboratory evolution of microbial co‐cultures for improved metabolite secretion

Adaptive laboratory evolution has proven highly effective for obtaining microorganisms with enhanced capabilities. Yet, this method is inherently restricted to the traits that are positively linked to cell fitness, such as nutrient utilization. Here, we introduce coevolution of obligatory mutualistic communities for improving secretion of fitness‐costly metabolites through natural selection. In this strategy, metabolic cross‐feeding connects secretion of the target metabolite, despite its cost to the secretor, to the survival and proliferation of the entire community. We thus co‐evolved wild‐type lactic acid bacteria and engineered auxotrophic Saccharomyces cerevisiae in a synthetic growth medium leading to bacterial isolates with enhanced secretion of two B‐group vitamins, viz., riboflavin and folate. The increased production was specific to the targeted vitamin, and evident also in milk, a more complex nutrient environment that naturally contains vitamins. Genomic, proteomic and metabolomic analyses of the evolved lactic acid bacteria, in combination with flux balance analysis, showed altered metabolic regulation towards increased supply of the vitamin precursors. Together, our findings demonstrate how microbial metabolism adapts to mutualistic lifestyle through enhanced metabolite exchange.     

Alterations in Ca2+ homeostasis in rat erythrocytes with atrazine treatment: positive modulation by vitamin E

Tubulin polymerization promoting protein 3 (TPPP3), a member of the TPPP family, can induce tubulin polymerization and microtubule bundling. Previously, it has been shown that TPPP3 plays an important role in cell proliferation. Depletion of TPPP3 by microRNA-based RNA interference (RNAi) inhibits cell growth, arrests cell cycles, and causes mitotic abnormalities in HeLa cells. In the present study, we knocked down TPPP3 in Lewis lung carcinoma (LLC) cells with the same RNAi construct, and observed a retarded tumor cell growth in vitro. Furthermore, C57BL/6 mice that received subcutaneously injected LLC cells in which TPPP3 was knocked down showed a pronounced reduction in tumor progression. The migration/invasion activity of TPPP3-knockdown LLC cells was significantly suppressed in a transwell chamber migration assay. When these cells were injected into the tail veins of C57BL/6 mice, they exhibited milder lung metastasis compared with control tumor cells. Taken together, these findings suggested that the TPPP3 gene played an important role in tumorigenesis and metastasis, and it could potentially become a novel target for cancer therapy.     

Class-specific restrictions define primase interactions with DNA template and replicative helicase

Bacterial primase is stimulated by replicative helicase to produce RNA primers that are essential for DNA replication. To identify mechanisms regulating primase activity, we characterized primase initiation specificity and interactions with the replicative helicase for gram-positive Firmicutes (Staphylococcus, Bacillus and Geobacillus) and gram-negative Proteobacteria (Escherichia, Yersinia and Pseudomonas). Contributions of the primase zinc-binding domain, RNA polymerase domain and helicase-binding domain on de novo primer synthesis were determined using mutated, truncated, chimeric and wild-type primases. Key residues in the β4 strand of the primase zinc-binding domain defined class-associated trinucleotide recognition and substitution of these amino acids transferred specificity across classes. A change in template recognition provided functional evidence for interaction in trans between the zinc-binding domain and RNA polymerase domain of two separate primases. Helicase binding to the primase C-terminal helicase-binding domain modulated RNA primer length in a species-specific manner and productive interactions paralleled genetic relatedness. Results demonstrated that primase template specificity is conserved within a bacterial class, whereas the primase–helicase interaction has co-evolved within each species.     

Visual deprivation suppresses L5 pyramidal neuron excitability by preventing the induction of intrinsic plasticity

In visual cortex monocular deprivation (MD) during a critical period (CP) reduces the ability of the deprived eye to activate cortex, but the underlying cellular plasticity mechanisms are incompletely understood. Here we show that MD reduces the intrinsic excitability of layer 5 (L5) pyramidal neurons and enhances long-term potentiation of intrinsic excitability (LTP-IE). Further, MD and LTP-IE induce reciprocal changes in K(v)2.1 current, and LTP-IE reverses the effects of MD on intrinsic excitability. Taken together these data suggest that MD reduces intrinsic excitability by preventing sensory-drive induced LTP-IE. The effects of MD on excitability were correlated with the classical visual system CP, and (like the functional effects of MD) could be rapidly reversed when vision was restored. These data establish LTP-IE as a candidate mechanism mediating loss of visual responsiveness within L5, and suggest that intrinsic plasticity plays an important role in experience-dependent refinement of visual cortical circuits.     

Evaluation of in vitro Probiotic Potential of Pediococcus pentosaceus OZF Isolated from Human Breast Milk

This study was conducted to evaluate the probiotic properties of Pediococcus pentosaceus OZF isolated from human breast milk. The results obtained so far suggest that the strain is resistant to low pH, bile salt, pepsin and pancreatin, so it could survive while passing through the upper part of the gastrointestinal tract and reveal its potential probiotic action on host organism. The strain was non-pathogenic (γ-hemolytic), produced anti-Listerial bacteriocin, exhibited a strong autoaggregating phenotype (85.71%) and demonstrated 6.26 and 12.99% coaggregation with Salmonella enterica serotype Typhimurium SL 1344 and Escherichia coli LMG 3083 (ETEC), respectively. The degree of adhesion of Ped. pentosaceus OZF to the human Caco-2 cell line was investigated and when compared to the adhesion of pathogenic strains tested, it was shown to inhibit the growth of human enterotoxigenic E. coli LMG 3083 (ETEC) and of Salm. Typhimurium SL 1344. Ped. pentosaceus OZF seems to adhere to human intestinal cells via mechanisms that involve different combinations of carbohydrate and lipid factors on the bacteria and eukaryotic cell surface. The percentage of adhesion to n-hexadecane was 34% showing that the surface was rather hydrophilic. Higher affinity displayed by Ped. pentosaceus OZF for chloroform demonstrates the basic property of a cell, which may be due to the presence of carboxylic groups on the cell surface.